Yin Yang 1 promotes aggressive cell growth in high-grade breast cancer by directly transactivating kinectin 1

Gao, Lin1; Zhou, Wenbin2; Xie, Ni3; Qiu, Junying4; Huang, Jingyi1; Zhang, Zhe1; Hong, Malin1,5; Xia, Jinquan1; Xu, Jing1; Zhao, Pan1,5; Fu, Li6,7; Luo, Yuwei2; Jiang, Jing8; Gong, Hui8; Wang, Jigang1,5; Dai, Yong1; Luo, Dixian8; Zou, Chang1,5,9

2022-09-01

10.1002/mco2.133

MEDCOMM   Impact Factor & Quartile

2688-2663

Invasive cancer growth and metastasis account for the poor prognosis of high-grade breast cancer. Recently, we reported that kinectin 1 (KTN1), a member of the kinesin-binding protein family, promotes cell invasion of triple-negative breast cancer and high-grade breast cancer cells by augmenting the NF-kappa B signaling pathway. However, the upstream mechanism regulating KTN1 is unknown. Therefore, this functional study was performed to decipher the regulatory cohort of KTN1 in high-grade breast cancer. Bioinformatic analysis indicated that transcription factor Yin Yang 1 (YY1) was a potential transactivator of KTN1. High YY1 expression correlated positively with pathological progression and poor prognosis of high-grade breast cancer. Additionally, YY1 promoted cell invasive growth both in vitro and in vivo, in a KTN1-dependent manner. Mechanistically, YY1 could transactivate the KTN1 gene promoter. Alternatively, YY1 could directly interact with a co-factor, DEAD-box helicase 3 X-linked (DDX3X), which significantly co-activated YY1-mediated transcriptional expression of KTN1. Moreover, DDX3X augmented YY1-KTN1 signaling-promoted invasive cell growth of breast cancer. Importantly, overexpression of YY1 enhanced tumor aggressive growth in a mouse breast cancer model. Our findings established a novel DDX3X-assisted YY1-KTN1 regulatory axis in breast cancer progression, which could lead to the development novel therapeutic targets for breast cancer.

breast cancer DDX3X growth invasion KTN1 YY1

ESCI

English

First ; Corresponding

Basic and Applied Basic Research Foundation of Guangdong Province["2020A1515111072","2020B1515120032","2020A1515011303"] ; Science and Technology Foundation of Shenzhen City["JCYJ20190806154610953","JCYJ20180305164128430"] ; Shenzhen Key Medical Discipline Construction Fund[SZXK053] ; Natural Science Foundation of Guangdong[JCYJ20180507182025817] ; International Cooperation Foundation of Shenzhen[GJHZ20180928171602104] ; Discipline Leadership Fund of Huazhong University of Science and Technology Union Shenzhen Hospital[YN2021002] ; National Natural Science Foundation of China[82002929,32070748,81972003]

Research & Experimental Medicine

Medicine, Research & Experimental

WOS:000820593200001

WILEY

Web of Science

1.Jinan Univ, Southern Univ Sci & Technol, Clin Med Coll 2,Affiliated Hosp 1, Dept Clin Med Res Ctr,Shenzhen Peoples Hosp, Shenzhen 518000, Guangdong, Peoples R China
2.Jinan Univ, Clin Med Coll 2, Dept Thyroid & Breast Surg,Southern Univ Sci & Te, Dept Gen Surg,Shenzhen Peoples Hosp,Affiliated Ho, Shenzhen, Guangdong, Peoples R China
3.Shenzhen Univ, Shenzhen Peoples Hosp 2, Hlth Sci Ctr, Affiliated Hosp 1,Biobank, Shenzhen, Guangdong, Peoples R China
4.Shenzhen Luohu Peoples Hosp, Med Lab, Shenzhen, Guangdong, Peoples R China
5.Jinan Univ, Clin Med Coll 2, Shenzhen Publ Serv Platform Tumor Precis Med & Mo, Shenzhen, Guangdong, Peoples R China
6.Shenzhen Univ Hlth Sci Ctr, Dept Pharmacol, Guangdong Prov Key Lab Reg Immun & Dis, Shenzhen, Guangdong, Peoples R China
7.Shenzhen Univ Hlth Sci Ctr, Int Canc Ctr, Shenzhen, Guangdong, Peoples R China
8.Huazhong Univ Sci & Technol, Dept Lab Med, Union Shenzhen Hosp, Nanshan Hosp, Shenzhen 518000, Guangdong, Peoples R China
9.Chinese Univ Kong Hong, Sch Life & Hlth Sci, Shenzhen, Guangdong, Peoples R China

Gao, Lin,Zhou, Wenbin,Xie, Ni,et al. Yin Yang 1 promotes aggressive cell growth in high-grade breast cancer by directly transactivating kinectin 1[J]. MEDCOMM,2022,3(3).

Gao, Lin.,Zhou, Wenbin.,Xie, Ni.,Qiu, Junying.,Huang, Jingyi.,...&Zou, Chang.(2022).Yin Yang 1 promotes aggressive cell growth in high-grade breast cancer by directly transactivating kinectin 1.MEDCOMM,3(3).

Gao, Lin,et al."Yin Yang 1 promotes aggressive cell growth in high-grade breast cancer by directly transactivating kinectin 1".MEDCOMM 3.3(2022).